Capping groups

The third NS3/4A inhibitor developed was SCH 503034 (boceprevir). This inhibitor also uses the keto-amide strategy to form a covalent bond with Serl39, and in this case representing a P1-P3 mimetic, although the P3 capping group occupies S4 (Venkatraman et al. 2006). An initial phase 1 dosing smdy showed potency in humans which was enhanced with coadministration of interferon-a (Sarrazin et al. 2007). 

Structure activity studies on compound (1), focusing on optimization at the 2-position of the quinoline and at the capping group, resulted in the... 

Fig. 19 Structure of LA-PRX (above) and degradation of LA-PRX (below), (a) Threaded a-CDs prevent hydrolysis of PLLA in LA-PRX. (b) LA-PRX converts into LA-pPRX by peptide linkage cleavage at bulky end-capping groups through action of papain, (c) Ester bond hydrolysis in the PLLA chain begins by an exposure of PLLA to water by release of a-CDs from LA-pPRX. Reprinted from [292] with permission...

In order to minimize peptide-like properties, macrocycles have been incorporated into these protease inhibitors. For example, connecting the P2 aryl side and P3 capping group gives 63, a 160 nM inhibitor (Kj) [121]. The optimal 17-membered macrocycle reportedly enhanced binding with NS3 by forming an... 

Control of the charge injection and transport by introduction of electron donor-acceptor substituents (or comonomers and end-capping groups)... 

Typical mass spectroscopy, AFM and gel electrophoresis (PAGE) results are shown in Table 27.2 for structures in the core-shell series [X] (Y)(Z) , where [X] = core, (Y) = shell, (Z) = capping groups and n = number of shell-type dendrimers bonded to the core (Table 27.2). 

Spindler and Frechet used 3,5-bis((benzoxy-carbonyl)imino)benzyl alcohol which decomposed thermally in THF solution containing DBTDL as a catalyst [97]. The resulting polymer was found to be insoluble unless an end-capping alcohol was added from the beginning. The end-capping groups determined the properties of the polymers such as glass transition temperature, thermal stability, and solubility. 

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